Delayed administration of angiotensin receptor (At2r) agonist c21 improves survival and preserves sensorimotor outcomes in female diabetic rats post-stroke through modulation of microglial activation

Ladonya Jackson-Cowan, Wael Eldahshan, Selin Dumanli, Guangkuo Dong, Sarah Jamil, Yasir Abdul, Waleed Althomali, Babak Baban, Susan C. Fagan, Adviye Ergul

Research output: Contribution to journalArticlepeer-review

Abstract

About 70% of stroke victims present with comorbid diseases such as diabetes and hy-pertension. The integration of comorbidities in pre-clinical experimental design is important in understanding the mechanisms involved in the development of stroke injury and recovery. We recently showed that administration of compound C21, an angiotensin II type 2 receptor agonist, at day 3 post-stroke improved sensorimotor outcomes by lowering neuroinflammation in diabetic male animals. In the current study, we hypothesized that a delayed administration of C21 would also lower chronic inflammation post-stroke in diabetic female animals. Young female diabetic rats were subjected to 1 h of middle cerebral artery occlusion (MCAO). Three days post-stroke, rats were administered C21 or vehicle in drinking water at a dose of 0.12 mg/kg/day for 4 weeks. The impact of C21 on microglial polarization was analyzed by flow cytometry in vivo and in vitro. Compound 21 treatment improved fine motor skills after MCAO through modulation of the microglia/macrophage inflammatory properties. In addition, C21 increased M2 polarization and reduced the M1:M2 ratio in vitro. In conclusion, delayed administration of C21 downregulates post-stroke inflammation in female diabetic animals. C21 may be a useful therapeutic option to lower neuro-inflammation and improve the post-stroke recovery in diabetes.

Original languageEnglish (US)
Article number1356
Pages (from-to)1-14
Number of pages14
JournalInternational journal of molecular sciences
Volume22
Issue number3
DOIs
StatePublished - Feb 1 2021
Externally publishedYes

Keywords

  • AT2 receptor
  • Diabetes
  • Ischemic stroke
  • Microglial polarization
  • Neuro-inflammation

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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